1. Field of the Invention
This invention relates generally to catheters capable of applying a chemical compound such as a drug or similar therapeutic agent to a remotely located tissue site through a restricted passage, and particularly to a low profile catheter system which utilizes light energy to selectively release that chemical compound.
2. Prior Art
Various catheters and related devices used to apply a drug or therapeutic compound to a specific tissue site are known to the art. Development of these systems has been most prevalent in the area of atherosclerosis treatment, particularly through percutaneous transluminal coronary angioplasty (PTCA) catheterization and related techniques.
Delivery of radiographic dyes and therapeutic compounds through the lumen and distal ports of angiography and angioplasty catheters has long been practiced. The technique has also been utilized in various thrombectomy, embolectomy, renal, esophageal, urethral, perfusion, and similar catheters both with and without dilation capabilities. U.S. Pat. No. 4,824,436 to Wolinsky is a representative example of a multiple-lumen dilation catheter designed to introduce heparin within a controlled region of the coronary vessel in order to inhibit smooth muscle cell hypertrophy or proliferation and therefore prevent restenosis. In addition to heparin, hirudin and its synthetic analogue fragment are often suggested to minimize hypertrophy, with antisense oligodeoxynucleotides also having been proposed. U.S. Pat. No. 4,994,033 to Shoekey similarly describes a system for releasing a liquid therapeutic agent directly through the dilation balloon of a coaxial over-the-wire PTCA catheter.
Dilation catheters having a coating which releases the therapeutic agent are also known. One representative example is U.S. Pat. No. 5,102,402 to Dror in which a microencapsulated compound is released upon expansion of the dilation balloon into contact with the surrounding tissue. Release is accomplished either by rupturing the microspheres upon contact with the arterial wall, or transfer of the microspheres to the arterial wall accompanied by subsequent degradation. Deformable porous microspheres could similarly be utilized in some applications, and U.S. Pat. No. 5,171,217 to March describes the delivery of several specific compounds through direct injection of microcapsules or microparticles using catheters of the type shown in Wolinsky '436.
U.S. Pat. No. 5,120,322 to Davis describes the process of coating the surface layer of a stent or shunt with a lathyrogenic agent to inhibit scar formation in the surrounding tissue during healing, thereby providing extended exposure to the therapeutic agent without requiring microencapsulation.
The use of electromagnetic energy--particularly in the form of microwave, radio frequency (rf), and coherent (laser) ultraviolet (uv) and visible-spectrum light energy within designated regions of the spectrum--has been adapted to angioplasty and atherectomy devices to accomplish a broad range of results.
U.S. Pat. No. 5,057,106 to Kasevich discloses the use of microwave energy for heating atherosclerotic plaque in the arterial wall in combination with dilation angioplasty. U.S. Pat. Nos. 4,807,620 to Strul and 5,087,256 to Taylor provide representative examples of atherectomy or angioplasty devices which convert electromagnetic rf energy to thermal energy. U.S. Pat. No. 5,053,033 to Clarke describes the use of an uv laser to inhibit restenosis by irradiation of smooth muscle cells with non-ablative cytotoxic light energy. U.S. Pat. Nos. 4,997,431 and 5,106,386 to Isner; 5,026,367 to Leckrone; 5,109,859 to Jenkins; and 4,846,171 to Kauphusman each disclose the use of laser light transmitted via an optical fiber or conduit to reduce tissue mass or remove arterial plaque by ablation. U.S. Pat. Nos. 4,878,492 to Sinofsky and 4,779,479 to Spears describe the use of nonablative laser light energy of sufficient wattage to heat the arterial plaque during a conventional PTCA dilation procedure in order to fuse fragmented plaque and coagulate trapped blood.
U.S. Pat. No. 5,100,429 to Sinofsky describes the process of forming a shunt in situ by applying a collagen-based adhesive to one side of a biologically-compatible sheet material, rolling that sheet material into a tube, positioning that tube at the selected site, and then applying light energy to crosslink the adhesive in order to bond the overlapping portions of the tube. A photodegradable adhesive coating may be used to initially secure the sheet material in position at the distal tip of a dilation catheter, with a second exposure of light energy at a discrete wavelength being used to release the crosslinked tube from the catheter. Similarly, U.S. Pat. No. 5,207,670 to Sinofsky describes the application of this principle to photoreactive suturing.
U.S. Pat. Nos. 5,092,84 1 and 5,199,951 to Spears each describe applying a coating of bioprotective material such as macroaggregated albumin or platelets to the external surface of a PTCA catheter, and then melting that coating and bonding it under pressure to the atherosclerotic lesion using thermal energy produced by laser light.
The various methods for introducing, delivering, or applying a drug or therapeutic agent to a specific site such as an atherosclerotic (stenotic) lesion or region of arterial plaque as described above have been shown to be beneficial, but each has concomitant problems or drawbacks.
Systems which deliver liquid agents or compounds within coronary arteries usually require either blocking a segment of the vessel for a prolonged period beyond that necessitated by the angioplasty procedure--after which the remaining agent is carried away by the bloodstream--or the use of relatively high and potentially damaging pressures to penetrate the arterial wall or plaque layer.
Microencapsulated coatings on catheters and stents permit longer exposure of the tissue to a particular compound or therapeutic agent, but the gross volume of the agent that can be effectively applied is significantly reduced due to the presence and limitations of the microcapsules themselves. Conversely, the concentration of the therapeutic agent can be increased, however this may result in exceeding the established protocols for such therapeutic agents to the point where patient-specific dosimetry can be required.
Exposed coatings generally require some type of sheath or shield that is removed from the catheter prior to the coating being melted or released. The sheath and any connections required to physically manipulate the sheath greatly increase the profile of the catheter, and limit the variety of applications for which such systems can be used. Moreover, the binders or adhesives used to formulate these coatings can account for the majority of their volume, and significantly dilute the concentration of the therapeutic agent.
The thermal and light energy required to melt and bond coatings such as macroaggregated albumin, to reduce tissue mass by ablation, and to inhibit restenosis by cytotoxic irradiation may also present concerns for damage to the arterial wall. These may include cytotoxic or cytogenic effects to healthy cells within (or even beyond) the tunica interna and tunica media, coagulation and subsequent release of incidental untrapped blood that may produce (or exacerbate) thrombosis or embolism, and similar deleterious results.